tbuckley/cabot-search huggingface dataset:
Additional cycles of docetaxel in combination with androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Efficacy and feasibility analysis.
Authors: Can Aydogdu, Florian Urban, Alexander Tamalunas, Elena Berg, Melanie Götz, Severin Rodler, Lena Unterrainer, Volker Heinemann, Christian G. Stief, Jozefina Casuscelli
Journal: Journal of Clinical Oncology (2023)

e17074 Background: Several phase III trials have assessed efficacy and safety of 6 cycles of docetaxel combined to androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). This is the current standard of care for a subgroup of patients. We aimed to assess whether treatment beyond 6 cycles of docetaxel prove to be more effective than the standard of care. Methods: We retrospectively collected data from patients with histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease treated at a large tertiary care center. All patients with mHSPC were treated in first-line with D-ADT (75 mg/m 2 ) intravenously on the first day of each 21-day cycle. A subset of patients was treated beyond the standard of 6 cycles. Clinical and pathological variables were examined, as were treatment-related toxicities; progression free survival on D-ADT (PFS1), progression free survival on subsequent therapy (PFS2) and overall survival (OS) were calculated from start of treatment to progression or death by log-rank test. Results: Between 2015-2023 a total of 108 mHSPC patients were treated and observed for a median time of 13.8 months. Mean age was 66.2 years (range 46.9-82.7), and 75.0% had GS≥8, 65.7% a CHAARTED high-volume and 69.4% LATITUDE high risk disease. 72 pts. were treated with ≤ 6 cycles (D-ADTstand) (4.2% 1-2 cycles; 95.8 % ≥3 cycles; mean 5.2 cycles) and 36 were treated with &gt; 6 cycles docetaxel (D-ADTadd) (27.8% 7-8 cycles; 72.2% ≥9-10 cycles, mean 9.2 cycles). Frequency of toxicities did not differ in the groups. No significant differences were observed in median PFS1 (10.3 vs. 13.4 mos.) and PFS2 (6.3 vs. 6.6 mos.). Median OS in the D-ADTstand group was 39.8 mos., median OS in the D-ADTadd group was not yet reached. Conclusions: While more than 6 cycles of D-ADT in mHSPC proved to be feasible without significant additional toxicity, efficacy is not superior compared to the standard of 6 cycles. Overall survival data is not mature yet, but the benefit of more chemotherapy upfront is debatable and leverages further studies in light of the upcoming triplet combinations in mHSPC, that presumably will render doublet D-ADT obsolete in future. [Table: see text]
Concurrent chemo-hormonal therapy of enzalutamide (ENZ) and cabazitaxel (CAB) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC): Final analysis of objective response rate (ORR), radiographic progression-free survival (rPFS), and overall survival (OS).
Authors: Alexandra Sokolova, Julie N. Graff, Claire E Smith, Tomasz M. Beer, Emile Latour, Petros Grivas, Michael Thomas Schweizer, Celestia S. Higano, Joshi J. Alumkal, Jacqueline Vuky, Evan Y. Yu, Heather H. Cheng
Journal: Journal of Clinical Oncology (2023)

5047 Background: We previously reported the PSA response rate and toxicity data of a phase 1/2 single-arm, multi-institutional trial to examine the efficacy and safety of co-administration of ENZ + CAB in mCRPC without prior chemotherapy given in the mCRPC setting. We found that full doses of ENZ (160 mg daily) and CAB (25 mg/m2) were tolerable and that 80% of pts had PSA decline ≥50%. Here, we report the final analysis of ORR, rPFS and OS. Methods: We calculated the ORR (CR/PR) and 95% confidence intervals using the Clopper-Pearson Exact Method. We determined response according to RECIST 1.1 for measurable disease and Prostate Cancer Working Group 2 criteria for non-measurable (bone) disease. We estimated median rPFS (time from the study entry to the time of confirmed progression (radiographic or clinical) or death) and OS (time from the study entry to death) with 95% confidence intervals using the Kaplan-Meier method; data cutoff was 6/1/22. Statistical analysis was performed using R: A language and environment for statistical computing. Results: 37 pts consented and 35 were included in the efficacy analyses (1 withdrew consent, 1 was lost to follow up before efficacy assessment); 7/35 (20%) had prior exposure to chemotherapy given for mHSPC and 9/35 (25%) had prior exposure to abiraterone (ABI), including 2/35 (25.7%) with prior exposure to chemotherapy and ABI. 28 pts had at least one on-study trial imaging study and were evaluable for ORR. After a median follow-up of 23.7 (range: 4.9 to 62.4) months (mo), median OS was 25.1 mo (95%CI 19.4 - 37.6 mo). Median PSA PFS was 11.9 mo (95%CI 9.2 - 15.4), and median rPFS was 22.2 mo (95%CI 13.6 - 25.2). PK assessments revealed that ENZ decreased CAB levels: CAB (monotherapy) Cmax 178.9ng*h/ml vs CAB (in the presence of ENZ) Cmax 85.5 ng*h/ml (p&lt;0.05). Conclusions: The combination of ENZ+CAB in this heterogeneous mCRPC population, which included about a quarter of pts with prior chemotherapy and ABI exposure, resulted in an OS of 22.5 mo comparing favorably with the OS of 25.2 mo seen in the FIRSTANA trial of single agent CAB in docetaxel naïve men, 15.1 mo post chemotherapy in the TROPIC trial, and 13.6 mo in the post-docetaxel, post-ABI in the CARD trial. Of note, the rPFS in this trial was 22.2 months compared to 5.1 months in FIRSTANA suggesting improved efficacy; however cross-trial comparisons are discouraged due to several confounders. Chemo-hormonal therapies and prognostic/predictive biomarkers warrant further study in mCRPC. Clinical trial information: NCT02522715 . [Table: see text]
Testicular GERM cell tumors treatment outcome in a national cancer institution in Peru.
Authors: Patricia Rioja, Guillermo Valencia, Zaida Morante, Hugo Fuentes, Raul Mantilla, Luis André Salinas Agramonte, Jorge Luis Sanchez Alarcon, Tatiana Vidaurre, Silvia P. Neciosup
Journal: Journal of Clinical Oncology (2023)

e17031 Background: Testicular germ cell tumor (TGCT) is the most common neoplasm in young men and the incidence has been increasing over the last few decades, especially among Hispanic men. Multidisciplinary management is associated with excellent oncological outcomes. Here, we describe the treatment outcome of TGCT patients treated in single institution in Peru. Methods: We conducted a retrospective study of TGCT treated at Instituto Nacional de Enfermedades Neoplasicas from 2016 to 2019. Clinical and pathological data were collected from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and compared with long-rank test. A level of p &lt; 0.05 was considered significant. The statistical package SPSS v19 was used for the data analysis. Results: 221 patients were identified, 56% were non-seminomatous (NS) and 44% were seminomatous (S). Orchiectomy was performed in 94% of patients, only 6% underwent orchiectomy after chemotherapy. In both groups, the treatment regimens were: BEP (Bleomycin/Etoposide/cisplatin) 90%, Carboplatin 8.1% and EP (Etoposide/Cisplatin) 1.8%. 42 (21%) of patients receive rescue therapy, being the most frequent TIP (paclitaxel/ifosfamide/cisplatin). In NS patients, 5-year PFS was superior in good risk compared with poor risk (100% vs. 86%, p = 0.028) and for tumor markers level, S0 was superior to S3 (100% vs. 82%, p = 0.008). In S, 5-year PFS was no significant in any of groups of analysis. With a median follow-up of 57 months, OS in NS was 91%, 83% and 81% in 12, 36 and 60 months, respectively and OS in S was 96%, 87% and 87% in 12, 36 and 60 months, respectively. The analysis of 5-year OS according to clinical stage and risk stratification are shown in the Table 1. Only 2 patients received high-dose chemotherapy and still in complete response. Conclusions: Despite the high incidence of advanced TGCT, our patients had excellent survival results; being lower in those with CS III (both NS and S groups), poor risk and S3 for NS, and intermediate risk for S. Multidisciplinary management in a high volume institution is important for better outcomes in our patients. [Table: see text]
Effects of the baseline prognostic factors on efficacy of the p62/SQSTM1-encoding plasmid combined with gemcitabine in patients with recurrent platinum-resistant ovarian cancer.
Authors: Alexander Shneider, Sergey Polyakov, Yauheni Baranau, Vlad Gabai, Ekaterina Zharkova, Olga Streltsova, Aliona Filimonava, Volha Siarheyeva, Sviatlana Kazlouskaya, Anton Khorau, Bhavana Pothuri, Sergei Krasny
Journal: Journal of Clinical Oncology (2023)

e17540 Background: We recently reported on the efficacy of the p62/SQTM1-encoding plasmid in patients with advanced, recurrent platinum-resistant ovarian cancer (PROC) receiving gemcitabine chemotherapy. Here we analyze the effects of baseline prognostic factors on efficacy. Methods: A prospective multicenter randomized study took place between 01/2020 and 08/2023. Cohort A (n=20) consisted of Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks and Cohort B (n=20) consisted of Gemcitabine (Gem) 1000 mg/m2 days 1,8 every 3 weeks plus p62-plasmid 2.5 mg i.m. weekly. We stratified the patients into subgroups according to their baseline CA-125 level (normal vs high), number of lines of chemo (1 vs 2-3) received by a platinum-sensitive ovarian cancer (PSOC) patient before they became PROC, platinum-free interval (PFI) (up to 3 mo vs more than 3 mo), and presence or absence of peritoneal effusion. Cox proportional hazards regression analysis was utilized to determine effect of progression free survival (PFS). Results: The median follow-up was 13.8 months (mos). The median PFS was 2.8 mos in Gem (Arm A) and 7.2 mos in Gem + Plasmid (Arm B) respectively (p = 0.03). The overall response rate (ORR) by RESIST 1.1 was higher in the Gem +Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, and disease control rate 41.2 and 80% in Chemo and Plasmid arms respectively). In cohort A, all patients have progressed, whereas in Cohort B (Gem +Plasmid) 9 patients (45%) remained progression-free with the longest duration of response being 30 mo. Overall survival cannot be assessed yet. Analyzing prognostic factors with Cox Proportional Hazards Regression Analysis identified that the following factors increase p62 sensitivity: initial high CA-125 level PFS 2.5 and 6.5 (p = 0.01) in Arm A vs B, 1 line chemo vs 2 or 3 lines for PSOC, PFS 2.3 and 7.1 (p = 0.008) in Arm A vs B, and presence of peritoneal effusion PFS 2.4 and 7.6 (p = 0.008) in Arm A vs B (Table ). Conclusions: We observed maximal effect on PFS when combining the p62-encoding plasmid with Gem in the patients with the most dismal prognosis PROC: rapid progression (relapse as PROC after the first line of treatment and/or short PFI), in patients with an initial high level of CA-125, and/or pleural effusion. [Table: see text]
Prognostic impact of hyponatremia in patients with pancreatic cancer: A nationwide analysis.
Authors: Vikash Kumar, Naresh Kumar, Bhavyakumar Vachhani, Surbhi Singh, Sidra Naz, Max Shulimovich
Journal: Journal of Clinical Oncology (2023)

e16304 Background: Hyponatremia has historically been reported to increase mortality and length of stay in hospitalized patients with solid tumors. There are sparse reports of hyponatremia linked to Pancreatic cancer in the published literature. Therefore, we evaluated mortality, morbidity, and resource utilization in Pancreatic cancer patients secondary to hyponatremia. Methods: A retrospective analysis was performed by utilizing the National Inpatient Sample database 2019 and the ICD- 10 codes to identify the patients &gt; 18 years old with the principal diagnosis of Pancreatic cancer. Effect of hyponatremia was studied on mortality, morbidity, and resource utilization. Categorical variables were compared using the chi-square test, and continuous variables were compared using the t- test. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Confounding variables were adjusted using multivariate logistic and linear regression analyses. These included: gender, race, Charlson Comorbidity Index, chronic kidney disease, congestive heart failure, cirrhosis, nephrotic syndrome, hypothyroidism, alcohol use disorder, and various patient and hospital characteristics. Results: We identified a total of 110,980 patients with primary diagnosis of pancreatic cancer in 2019, Of whom 18.1% (5,845) had hyponatremia on presentation. Patients with hyponatremia had 9.48 % in-hospital mortality, while 6.68% for patients without hyponatremia. After adjusting for confounders, hyponatremia imparted higher odds of mortality (Adjusted odds ratio (aOR) for mortality 1.46, 95% confidence interval (CI): 1.28–1.67, P&lt; 0.01). Pancreatic cancer patients with hyponatremia have higher odds of Sepsis (Odd ratio = 1.64), Acute kidney injury (Odd ratio = 2.03), Peritonitis (Odd ratio = 2.40), and ICU admission (Odd ratio = 3.82). Hyponatremia also resulted in higher resource utilization marked by the length of stay, and hospital charges, (higher mean LOS by 1.16 days, and higher mean total hospital charges by $ 12,320). Conclusions: Hyponatremia in Pancreatic cancer patients had a prevalence of 18.1% and resulted in increased in-hospital mortality. Whether time-efficient treatment of hyponatremia would help reduce mortality and improve outcomes remains to be determined in future studies. [Table: see text]
Efficacy and safety of immunonutrition in preventing oral mucositis during concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.
Authors: Yating Qin, Chaolin Yang, Dong Yang, Zhen Meng, Huan Dong, Pian Li, Heqing Huang, Xueying Hu, Tingting Zhang, Meizhu Shen, Kang Liu, Yeying Fang, Rensheng Wang, Min Kang
Journal: Journal of Clinical Oncology (2023)

e18056 Background: To assess the efficacy of immunonutrition on severe radiotherapy-induced mucositis (RIOM) during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC). Methods: In total, 30 patients with NPC undergoing CCRT were enrolled in our study. Patients in immunonutrition group (n = 15) receive an immunonutrient formula containing omega-3-fatty acids, arginine, nucleotides from five days before radiotherapy until the end of radiotherapy. Patients in control group (n = 15) receive isocaloric isonitrogenous product. The incidence of grade 3 or 4 RIOM was compared between two groups. Results: Although there was no difference of the incidence of grade 3-4 oral mucositis between the two groups (p = 0.050), the rate of severe mucositis were 13.3% (2/15) in immunonutrients, which was much lower than 53.33% (8/15) in control group. A significant improvement in body fat mass was observed in immunonutrition group than that in control group during the CCRT (3.476, 95CI% 0.015~6.937, P = 0.049) and at the end of CCRT (4.115, 95%CI 0.872~7.359, p = 0.015). And the levels of interleukin 6 (-6.765, 95%CI -16.104~2.573, p = 0.148) and C-reactive protein (CRP) (-7.937, 95%CI -20.395~4.520, p = 0.201) at the end of radiotherapy were lower in immunonutritions even though no statistical difference was reached. In addition, immunonutrition has the potential to improve the life of the patient in the EORTC QLQ-H&amp;N35 scales in painkillers (-13.332, 95%CI -22.612~-4.052, p = 0.007), pain (-15.873, 95%CI -32.131~0.384, p = 0.055), dysphagia (-15.516, 95%CI -34.136~3.104, p = 0.099) and dry mouth (-12.860, 95%CI -31.135~5.415, p = 0.160) at the end of radiotherapy. No patients died of treatment-related causes. Conclusions: Our study indicates that immunonutrition may reduce severe oral mucositis and improved quality of life for patients with NPC during CCRT. Further studies with a larger sample size on the role of immunonutrition in oral mucositis are required to substantiate the result of the study.
Cost-effectiveness of novel systemic therapies for advanced breast cancer: Global representativeness and influence of funding.
Authors: Felippe Lazar Neto, Marina Melo, Cassio Murilo Trovo Hidalgo Filho, Maria Cecilia Mathias, Laura Testa, Alessandro Campolina
Journal: Journal of Clinical Oncology (2023)

e18924 Background: Approval of expensive novel treatments increases costs of cancer care and undermines access, particularly in low and middle-income countries. As the most incident neoplasm, breast cancer (BC) therapies have an enormous budget impact if incorporated. Therefore, cost-effectiveness (CE) studies are essential to guide such decisions. Methods: A systematic literature search of Medline, Scopus, and Web of Science from January 1 st 2012 to July 8 th 2022 was conducted to identify CE studies of tumor-targeted systemic therapies for advanced BC. Articles without CE (or utility) ratio calculations were excluded. Information on the country and drug studied, authors’ conflicts of interests (COI) and funding, and authors' conclusions were manually reviewed by two independent investigators. Results: Of 1103 screened records, 74 studies comprising 212 CE comparisons were included. Most studied scenarios were from high-income countries (70%, 141/212), with only 10% from Latin America and none from Africa. The most studied drug classes were iCDK4/6 (23%), anti-HER2 directed therapy (21%), anti-PD1/PDL1 (12%) and endocrine therapy (11%). In 46% of the comparisons, a new drug combined with standard of care was compared to placebo and/or standard of care, and in 37% the compared treatment were alternative same class therapies. Nearly 46% (97/212) had pharmaceutical industry funding or author’s COI associated with industry. Overall, 56% of authors’ conclusions were unfavorable. Pharmaceutical industry related-studies were associated with high-income countries (75% vs. 64%, p = 0.006), same-class drug comparators (52% vs. 33%, p = 0.047), and favorable conclusions (60% vs. 15%, p &lt; 0.001). A combination of drugs (addition to standard of care) was associated with unfavorable conclusions (56% vs 28%, p &lt; 0.001). Conclusions: Industry-related studies target high-income countries' scenarios and are more likely to have favorable conclusions. As expected, the addition of drugs to standard treatments (combinations) is less likely to be cost-effective. Government funding in low and middle-income countries is needed to decrease the current literature gap and provide stakeholders with proper information to make incorporation decisions.
Medication acquisition program: Successful access to innovative treatment options.
Authors: Vicki Doctor, Julian C. Schink, Amber Moran, Neha Gandra, Maurie Markman
Journal: Journal of Clinical Oncology (2023)

e18521 Background: Targeted treatments are often not available due to clinical, financial, and administrative barriers. Our medication acquisition program (MAP) serves our national network of cancer centers, helping patients gain access to off-label and scientifically appropriate targeted therapy and immunotherapy when access was unavailable due to the following barriers: clinical trial not available, patients with government insurance unable to afford copay, or insurance policy exclusion or denial for an off-label or on-label indication. The use of genomic testing is used increasingly to identify candidates for clinical trials. While our patients are always offered a clinical trial when available, they don’t always qualify. The goal of this study was to examine our success rate in acquiring medications and the clinical outcomes of those therapies. Methods: An IRB approved retrospective review was completed on patients who accessed targeted treatments that had an existing standard of care (SOC) indication in another tumor type or were being denied access for their on-label indication. For purposes of this study, we defined clinical benefit as treatment duration of 4 months or greater. Results: 1,041 referrals were received by our program between 10/1/2015 and 12/31/2021. While not all therapies referred and accessed were started, we have maintained a 99% success rate for access to these therapies with one dedicated oncology nurse. All therapies started were accessed through appeals to payers or through patient assistance programs. Of the 769 patients who started treatment, 507 (66%) were on therapy for 3 months or less, 120 (16%) were on therapy for 4 to 6 months, 64 (8%) were on therapy for 7 to 10 months, and 78 (10%) were on therapy for 11 months or more. 342 of patients starting therapy through MAP went on to progress and of those, 231 (68%) were able to receive another treatment for their cancer and continue treating at our center. Overall, this process has demonstrated a clinical benefit for 262 (34%) patients who were able to stay on therapy for four months or longer. Conclusions: A process for medication access overseen by one oncology certified nurse highly skilled and knowledgeable of access process as well as a lean methodology for execution has made innovative options for precision care accessible to 769 patients with advanced cancer. The number of patients who access and start treatment combined with the overall clinical benefit for these patients demonstrate how this efficient process, facilitated by nominal FTEs, can enable successful alternate access for patients seeking options. Our medication acquisition program has provided our patients access to targeted treatments that would have otherwise not been available while enhancing our center’s ability to offer innovative options to patients who have exhausted SOC options.